The overarching goal of this renewal application (R01DA033862) is to determine the influence of structural interventions on engagement in risk reduction and health promotion activities among rural Appalachian drug users. Results from the three-year R01 that the investigators seek to continue reveal an ever-changing landscape of prescription drug abuse; an epidemic that is still in its infancy. Unlike many rural and suburban areas, there is little evidence for the transition to heroin abuse. In this cohort, there has been marked shift from abuse of OxyContin(r) (extended-release oxycodone) to immediate release oxycodone to more recently, buprenorphine and gabapentin-containing products. In addition, rates of HCV prevalence and incidence are high, especially given the population density of rural Appalachia. Given the syndemic of opioid abuse and infectious disease transmission, two structural interventions are particularly relevant to this population of rural people who use drugs (PWUD). Medicaid (MC) expansion (under the Affordable Care Act [ACA]) and syringe access programs (SAP) are two structural interventions that may allow for increased engagement in health promotion among PWUD, but are likely heavily influenced by individual, network, and community-level factors. Utilizing Latkin's Dynamic Social Systems model and leveraging the extant, highly successful cohort of rural PWUD, the aims include: 1) examining how dynamic factors of these structural interventions influence longitudinal trends in illicit and prescription drug abuse; 2) determining the influence of these structural interventions on HIV/HCV incidence and engagement in risk reduction; and 3) assessing the influence of these structural interventions on uptake of substance abuse treatment. This study is highly significant given that understanding the mechanisms by which these specific structural interventions influence health promotion is key to improving public health in rural Appalachia. Substance abuse and HCV are two of the most important, if not the most important health issues facing this region already plagued with marked health disparities. Using innovative measures of network and geospatial risk, as well as conjoint analysis and multilevel longitudinal statistical models, results will not only inform development of interventions that optimize uptake and utilization of risk reduction services such as SAP and substance abuse treatment, but may inform policies surrounding further implementation of health promotion programs in the rural U.S.